rs542967776

Variant names:

• chr10-133127325-C-A
• NM_001083909.3:c.494C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-133127325-C-A
• chr10-133127325-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001083909.3(ADGRA1):​c.494C>A​(p.Thr165Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T165M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRA1 NM_001083909.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

Genes affected

ADGRA1 (HGNC:13838): (adhesion G protein-coupled receptor A1) This gene encodes a protein that belongs to the adhesion family of G-protein-coupled receptors. Members of this family function in several sensory systems and regulate blood pressure, immune responses, food intake and development. A similar protein in rodents is thought to play a role in in the regulation of neuronal signaling pathways. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.117541194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRA1	NM_001083909.3	c.494C>A	p.Thr165Lys	missense_variant	Exon 6 of 7	ENST00000392607.8	NP_001077378.1
ADGRA1	NM_001291085.2	c.203C>A	p.Thr68Lys	missense_variant	Exon 3 of 4		NP_001278014.1
ADGRA1	XM_011540273.1	c.-14C>A		5_prime_UTR_variant	Exon 2 of 3		XP_011538575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRA1	ENST00000392607.8	c.494C>A	p.Thr165Lys	missense_variant	Exon 6 of 7	5	NM_001083909.3	ENSP00000376384.3
ADGRA1	ENST00000392606.2	c.203C>A	p.Thr68Lys	missense_variant	Exon 3 of 4	1		ENSP00000376383.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.038	.;T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.19	T;T;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.2	.;N;.
REVEL	Benign	0.053
Sift	Benign	0.081	.;T;.
Sift4G	Benign	0.12	T;D;D
Polyphen		0.79	P;B;.
Vest4		0.30
MutPred		0.55		.;Gain of ubiquitination at T165 (P = 0.0192);.;
MVP		0.093
MPC		0.69
ClinPred		0.23	T
GERP RS		1.6
Varity_R		0.042
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-134940829;